Characterization of expression and alternative splicing of the gene cadherin-like and PC esterase domain containing 1 (Cped1)
Characterization of expression and alternative splicing of the gene cadherin-like and PC esterase domain containing 1 (Cped1)
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DOI：
10.1016/j.gene.2018.06.060
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发表时间：
2018-10-20
期刊：
影响因子：
3.5
通讯作者：
Ackert-Bicknell, Cheryl L.
中科院分区：
文献类型：
--
作者：
Maynard, Robert D.;Godfrey, Dana A.;Ackert-Bicknell, Cheryl L.
钙粘蛋白样和PC酯酶结构域1（CPED 1）是一个功能未知的基因。骨矿物质密度（BMD）的人类全基因组关联研究（GWAS）多次确定了7号染色体上含有基因CPED 1的重要位点，但尚不清楚该基因是否可能是致病基因。虽然这个基因的开放阅读框架已被预测，有没有系统的探索在人类或小鼠CPED 1的表达或选择性剪接。使用小鼠模型，我们证明，Cped1是选择性剪接，从而产生转录本与外显子3或外显子16和17删除。在颅骨来源的前成骨细胞中，Cped1利用了外显子1上游的预测启动子以及外显子3和外显子12上游的交替启动子。最后，我们确定了一些转录本终止于外显子10的末端，因此不包含钙粘蛋白样结构域和PC酯酶结构域。这些数据表明，该基因可能产生多种蛋白产物，有些产物缺乏或含有两种预测的功能结构域。我们的数据提供了一个框架，未来的功能研究将建立在了解该基因在骨生物学中的作用。
Cadherin-like and PC-esterase domain containing 1 (CPED1) is an uncharacterized gene with no known function. Human genome wide association studies (GWAS) for bone mineral density (BMD) have repeatedly identified a significant locus on Chromosome 7 that contains the gene CPED1, but it remains unclear if this gene could be causative. While an open reading frame for this gene has been predicted, there has been no systematic exploration of expression or alternate splicing for CPED1 in humans or mice.Using mouse models, we demonstrate that Cped1 is alternately spliced whereby transcripts are generated with exon 3 or exons 16 and 17 removed. In calvarial-derived pre-osteoblasts, Cped1 utilizes the predicted promoter upstream of exon 1 as well as alternate promoters upstream of exon 3 and exon 12.Lastly, we have determined that some transcripts terminate at the end of exon 10 and therefore do not contain the cadherin like and the PC esterase domains.Together, these data suggest that multiple protein products may be produced by this gene, with some products either lacking or containing both the predicted functional domains. Our data provide a framework upon which future functional studies will be built to understand the role of this gene in bone biology.